Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3

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• 作者：Xiao‐ting Zhu ; Ji‐hang Yuan ; Teng‐teng Zhu ; Yang‐yang Li ; Xiao‐yang Cheng
• 刊名：FEBS Journal
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：283
• 期：20
• 页码：3739-3754
• 全文大小：1.7MB
• ISSN：1742-4658

文摘

Long noncoding RNA (lncRNA) have critical roles in various pathophysiological processes, and are frequently dysregulated in many diseases, particularly in cancer. The lncRNA glypican 3 antisense transcript 1 (GPC3-AS1) has been reported to be a potential biomarker for hepatocellular carcinoma (HCC) screening. However, the exact biological functions of GPC3-AS1 in HCC, and its roles and regulation mechanisms regarding GPC3 are still unknown. In this study, we observed a significant upregulation of GPC3-AS1 in HCC. Increased expression of GPC3-AS1 was associated with α-fetoprotein, tumor size, microvascular invasion, encapsulation, Barcelona Clinic Liver Cancer stage, and worse prognosis of HCC patients. Furthermore, we found that GPC3-AS1 physically associated with P300/CBP-associated factor and recruited it to the GPC3 gene body region, consequently inducing an increase in euchromatic histone marks and activating GPC3 transcription. GPC3-AS1 expression was strongly correlated with GPC3 in HCC tissues. Gain-of-function and loss-of-function analyses showed that GPC3-AS1 overexpression enhanced HCC cell proliferation and migration in vitro and xenograft tumor growth in vivo. GPC3-AS1 knockdown inhibited HCC cell proliferation and migration. Moreover, the effects of GPC3-AS1 on HCC cell proliferation and migration were dependent on the upregulation of GPC3. Collectively, our studies indicate that GPC3-AS1 significantly promotes HCC progression via epigenetically activating GPC3, and identifies GPC3-AS1 as a potential therapeutic target for HCC.